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Vascular alterations in PDAPP mice after anti-Aβ immunotherapy: Implications for amyloid-related imaging abnormalities
Zago W, Schroeter S, Guido T, Khan K, Seubert P, Yednock T, Schenk D, Gregg KM et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2013-04-11
Topic: Plasma and spinal-fluid biomarkers
Background Clinical studies of β-amyloid (Aβ) immunotherapy in Alzheimer's disease (AD) patients have demonstrated reduction of central Aβ plaque by positron emission tomography (PET) imaging and the appearance of amyloid-related imaging abnormalities (ARIA). To better understand the relationship between ARIA and the pathophysiology of AD, we undertook a series of studies in PDAPP mice evaluating vascular alterations in the context of central Aβ pathology and after anti-Aβ immunotherapy. Methods We analyzed PDAPP mice treated with either 3 mg/kg/week of 3D6, the murine form of bapineuzumab, or isotype control antibodies for periods ranging from 1 to 36 weeks and evaluated the vascular alterations in the context of Aβ pathology and after anti-Aβ immunotherapy. The number of mice in each treatment group ranged from 26 to 39 and a total of 345 animals were analyzed. Results The central vasculature displayed morphological abnormalities associated with vascular Aβ deposits. Treatment with 3D6 antibody induced clearance of vascular Aβ that was spatially and temporally associated with a transient increase in microhemorrhage and in capillary Aβ deposition. Microhemorrhage resolved over a time period that was associated with a recovery of vascular morphology and a decrease in capillary Aβ accumulation. Conclusions These data suggest that vascular leakage events, such as microhemorrhage, may be related to the removal of vascular Aβ. With continued treatment, this initial susceptibility period is followed by restoration of vascular morphology and reduced vulnerability to further vascular leakage events. The data collectively suggested a vascular amyloid clearance model of ARIA, which accounts for the currently known risk factors for the incidence of ARIA in clinical studies.
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APA 7th
Zago, W., Schroeter, S., Guido, T., Khan, K., Seubert, P., Yednock, T., et al. (2013). Vascular alterations in PDAPP mice after anti-Aβ immunotherapy: Implications for amyloid-related imaging abnormalities. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1016/j.jalz.2012.11.010
Vancouver
Zago W, Schroeter S, Guido T, Khan K, Seubert P, Yednock T, et al. Vascular alterations in PDAPP mice after anti-Aβ immunotherapy: Implications for amyloid-related imaging abnormalities. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2013. doi:10.1016/j.jalz.2012.11.010. PMID: 23583235.
BibTeX
@article{zago2013-23583235,
author = {Zago, W. and Schroeter, S. and Guido, T. and Khan, K. and Seubert, P. and Yednock, T. and Schenk, D. and Gregg, K. M. and others},
title = {{Vascular alterations in PDAPP mice after anti-Aβ immunotherapy: Implications for amyloid-related imaging abnormalities}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2013},
doi = {10.1016/j.jalz.2012.11.010},
pmid = {23583235},
url = {https://doi.org/10.1016/j.jalz.2012.11.010}
}
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Key findings
- Background Clinical studies of β-amyloid (Aβ) immunotherapy in Alzheimer's disease (AD) patients have demonstrated reduction of central Aβ plaque by positron emission tomography (PET) imaging and the appearance of amyloid-related imaging abnormalities (ARIA).
- Results The central vasculature displayed morphological abnormalities associated with vascular Aβ deposits.
- Treatment with 3D6 antibody induced clearance of vascular Aβ that was spatially and temporally associated with a transient increase in microhemorrhage and in capillary Aβ deposition.
- Microhemorrhage resolved over a time period that was associated with a recovery of vascular morphology and a decrease in capillary Aβ accumulation.
- Conclusions These data suggest that vascular leakage events, such as microhemorrhage, may be related to the removal of vascular Aβ.
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Study details
- Participants345
- Evidence strengthLow
How this study scored 43/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 25 of the 58 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2013 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 345 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mice”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23583235) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 25 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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